Worsening of Heart Failure in Outpatients With Transthyretin Amyloidosis and Cardiomyopathy in the APOLLO-B Trial

Background

Outpatient worsening heart failure (HF), defined by initiation or intensification of diuretics, is adversely prognostic for patients with either reduced or preserved ejection fraction.

Objectives

This study sought to investigate the prognostic value of outpatient worsening HF in transthyretin amyloidosis with cardiomyopathy and the effect of patisiran treatment.

Methods

Post hoc analyses of the APOLLO-B trial (NCT03997383) evaluated the associations between outpatient worsening HF (defined by oral diuretic initiation or intensification), measures of disease progression, and a composite endpoint of all-cause mortality and cardiovascular (CV) events. We further examined the effect of patisiran on outpatient worsening HF over 24 months (ie, during the double-blind and open-label extension periods).

Results

In APOLLO-B, 144 (40.1%) patients had no event, 157 (43.7%) had outpatient worsening HF, 13 (3.6%) required an urgent HF visit, 118 (32.9%) had a CV hospitalization, and 47 (13.1%) died. Outpatient worsening HF was associated with an increased risk of all-cause mortality and CV events (HR: 2.21; 95% CI: 1.58-3.08), as well as a greater deterioration in 6-minute walk test distance, Kansas City Cardiomyopathy Questionnaire–Overall Summary score, and NYHA functional class and a greater increase in N-terminal prohormone of B-type natriuretic peptide. Addition of outpatient diuretic initiation or intensification to the composite endpoint of all-cause mortality and CV events increased the overall number of patients having an event from 141 to 215 (a 52% increase). Patisiran reduced the risk of outpatient worsening HF (HR: 0.70; 95% CI: 0.51-0.96) over 24 months.

Conclusions

During APOLLO-B, outpatient worsening HF in patients with transthyretin amyloidosis with cardiomyopathy was frequent, prognostic, and reduced by patisiran.